Brain Organoids: Studying Human Brain Development and Diseases in a Dish.
Ontology highlight
ABSTRACT:
SUBMITTER: Xu J
PROVIDER: S-EPMC8448601 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:This SuperSeries is composed of the SubSeries listed below.
2019-06-01 | GSE132026 | GEO
Project description:Human pluripotent stem cells (hPSCs)-derived kidney organoids recapitulate complex developmental processes and tissue architectures, but the intrinsic limitations, such as variability and a lack of vasculature, have greatly hampered their application. Here we establish a highly efficient and versatile protocol for generating vascularized three-dimensional (3D) kidney organoids. We employ dynamic modulation of WNT signaling to control the relative proportion of proximal versus distal nephron segments, thereby producing a correlative level of VEGFA to define the resident vascular network. By single cell RNA-sequencing, we identify a subset of nephron progenitor cells as a potential source of the vasculature. Upon implantation into host mice, these kidney organoids undergo further structural and functional maturation, as demonstrated by the size-selective handling of dextran. Based on this differentiation platform, we establish an in vitro model of autosomal recessive polycystic kidney disease (ARPKD) by differentiating induced PSCs (iPSCs) from an ARPKD patient into 3D kidney organoids that develop tubule cysts in response to cAMP upregulation. The cystogenesis phenotype can be effectively prevented by gene correction or drug treatment. Our studies provide a versatile platform for studying human kidney development and diseases, and opens new avenues for modeling disease pathogenesis and performing patient-specific drug screening.
2019-06-01 | GSE132023 | GEO
Project description:Human pluripotent stem cells (hPSCs)-derived kidney organoids recapitulate complex developmental processes and tissue architectures, but the intrinsic limitations, such as variability and a lack of vasculature, have greatly hampered their application. Here we establish a highly efficient and versatile protocol for generating vascularized three-dimensional (3D) kidney organoids. We employ dynamic modulation of WNT signaling to control the relative proportion of proximal versus distal nephron segments, thereby producing a correlative level of VEGFA to define the resident vascular network. By single cell RNA-sequencing, we identify a subset of nephron progenitor cells as a potential source of the vasculature. Upon implantation into host mice, these kidney organoids undergo further structural and functional maturation, as demonstrated by the size-selective handling of dextran. Based on this differentiation platform, we establish an in vitro model of autosomal recessive polycystic kidney disease (ARPKD) by differentiating induced PSCs (iPSCs) from an ARPKD patient into 3D kidney organoids that develop tubule cysts in response to cAMP upregulation. The cystogenesis phenotype can be effectively prevented by gene correction or drug treatment. Our studies provide a versatile platform for studying human kidney development and diseases, and opens new avenues for modeling disease pathogenesis and performing patient-specific drug screening.
2019-05-29 | GSE131841 | GEO
Project description:The complexity of the human brain has made it difficult to study many brain disorders in model organisms, highlighting the need for an in vitro model of human brain development. Here we have developed a human pluripotent stem cell-derived three-dimensional organoid culture system, termed cerebral organoids, that develop various discrete, although interdependent, brain regions. These include a cerebral cortex containing progenitor populations that organize and produce mature cortical neuron subtypes. Furthermore, cerebral organoids are shown to recapitulate features of human cortical development, namely characteristic progenitor zone organization with abundant outer radial glial stem cells. Finally, we use RNA interference and patient-specific induced pluripotent stem cells to model microcephaly, a disorder that has been difficult to recapitulate in mice. We demonstrate premature neuronal differentiation in patient organoids, a defect that could help to explain the disease phenotype. Together, these data show that three-dimensional organoids can recapitulate development and disease even in this most complex human tissue.
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Project description:Generating Patterned Kidney Organoids for Studying Development and Diseases
| PRJNA545689 | ENA
Project description:Thalamus is a critical information relay hub in the cortex; its malfunction causes multiple neurological and psychiatric disorders. However, there are no model systems to study the development and function of human thalamus. Here, we present a protocol to generate regionally specified human brain organoids that recapitulate the development of the thalamus using human pluripotent stem cells (hPSCs). Thalamic organoids can be used to study human thalamus development, to model related diseases, and to discover potential therapeutics. For complete information on human thalamic organoids and their application, please refer to the paper by Xiang et al. (2019).
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Project description:Human liver infection is a major cause of death worldwide, but fundamental studies on infectious diseases affecting humans have been hampered by the lack of robust experimental models that accurately reproduce pathogen-host interactions in an environment relevant for the human disease. In the case of liver infection, one consequence of this absence of relevant models is a lack of understanding of how pathogens cross the sinusoidal endothelial barrier and parenchyma. To fill that gap we elaborated human 3D liver in vitro models, composed of human liver sinusoidal endothelial cells (LSEC) and Huh-7 hepatoma cells as hepatocyte model, layered in a structure mimicking the hepatic sinusoid, which enable studies of key features of early steps of hepatic infection. Built with established cell lines and scaffold, these models provide a reproducible and easy-to-build cell culture approach of reduced complexity compared to animal models, while preserving higher physiological relevance compared to standard 2D systems. For proof-of-principle we challenged the models with two hepatotropic pathogens: the parasitic amoeba Entamoeba histolytica and hepatitis B virus (HBV). We constructed four distinct setups dedicated to investigating specific aspects of hepatic invasion: 1) pathogen 3D migration towards hepatocytes, 2) hepatocyte barrier crossing, 3) LSEC and subsequent hepatocyte crossing, and 4) quantification of human hepatic virus replication (HBV). Our methods comprise automated quantification of E. histolytica migration and hepatic cells layer crossing in the 3D liver models. Moreover, replication of HBV virus occurs in our virus infection 3D liver model, indicating that routine in vitro assays using HBV or others viruses can be performed in this easy-to-build but more physiological hepatic environment. These results illustrate that our new 3D liver infection models are simple but effective, enabling new investigations on infectious disease mechanisms. The better understanding of these mechanisms in a human-relevant environment could aid the discovery of drugs against pathogenic liver infection.
| S-EPMC4749187 | biostudies-literature
Project description:The establishment of robust human brain organoids to model cerebellar diseases is essential to study new therapeutic strategies for cerebellum-associated disorders. Machado-Joseph disease (MJD) is a cerebellar hereditary neurodegenerative disease, without therapeutic options able to prevent the disease progression. In the present work, control and MJD induced-pluripotent stem cells were used to establish human brain organoids. These organoids were characterized regarding brain development, cell type composition, and MJD-associated neuropathology markers, to evaluate their value for cerebellar diseases modeling. Our data indicate that the organoids recapitulated, to some extent, aspects of brain development, such as astroglia emerging after neurons and the presence of ventricular-like zones surrounded by glia and neurons that are found only in primate brains. Moreover, the brain organoids presented markers of neural progenitors proliferation, neuronal differentiation, inhibitory and excitatory synapses, and firing neurons. The established brain organoids also exhibited markers of cerebellar neurons progenitors and mature cerebellar neurons. Finally, MJD brain organoids showed higher ventricular-like zone numbers, an indication of lower maturation, and an increased number of ataxin-3-positive aggregates, compared with control organoids. Altogether, our data indicate that the established organoids recapitulate important characteristics of human brain development and exhibit cerebellar features, constituting a resourceful tool for testing therapeutic approaches for cerebellar diseases.
| S-EPMC9307606 | biostudies-literature
Project description:<p>Human brain organoids are emerging models to study human brain development and pathology as they recapitulate the development and characteristics of major neural cell types, and enable manipulation through an <em>in vitro</em> system. Over the past decade, with the advent of spatial technologies, mass spectrometry imaging (MSI) has become a prominent tool for metabolic microscopy, providing label-free, non-targeted molecular and spatial distribution information of the metabolites within tissue, including lipids. This technology has never been used for studies of brain organoids and here, we set out to develop a standardized protocol for preparation and mass spectrometry imaging of human brain organoids. We present an optimized and validated sample preparation protocol, including sample fixation, optimal embedding solution, homogenous deposition of matrices, data acquisition and processing to maximize the molecular information derived from mass spectrometry imaging. We focus on lipids in organoids, as they play critical roles during cellular and brain development. Using high spatial and mass resolution in positive- and negative-ion modes, we detected 260 lipids in the organoids. Seven of them were uniquely localized within the neurogenic niches or rosettes as confirmed by histology, suggesting their importance for neuroprogenitor proliferation. We observed a particularly striking distribution of ceramide-phosphoethanolamine CerPE 36:1; O2 restricted within rosettes and of phosphatidyl-ethanolamine PE 38:3, which was distributed throughout the organoid tissue but not in rosettes. This suggests that ceramide in this particular lipid species might be important for neuroprogenitor biology, while its removal may be important for terminal differentiation of their progeny. Overall, our study establishes the first optimized experimental pipeline and data processing strategy for mass spectrometry imaging of human brain organoids, allowing direct comparison of lipid signal intensities and distributions in these tissues. Further, our data shed new light on the complex processes that govern brain development by identifying specific lipid signatures that may play a role in metabolic cell fate trajectories. mass spectrometry imaging thus has great potential in advancing our understanding of early brain development as well as disease modeling and drug discovery.</p>
2023-05-23 | MTBLS7565 | MetaboLights
Project description:Generating Patterned Kidney Organoids for Studying Development and Diseases [scRNA-Seq]
| PRJNA545652 | ENA